The efficacy and safety of itopride as an add-on therapy to a proton pump inhibitor in the treatment of gastroesophageal reflux disease.

Introduction: The primary objective was to demonstrate the efficacy and safety of itopride as an add-on therapy to a proton pump inhibitor (PPI) in the treatment of gastroesophageal reflux disease. Aim: Reflux disease affects the largest percentage of the population worldwide, symptoms overlap with many other conditions which hamper diagnostic and therapy presenting challenges in treating patients and prompting an intensive search for new, more effective therapeutic regimens. Material and methods: A retrospective study was undertaken with 140 enrolled patients with reflux disease, confirmed by 24-hour pH impedance previously treated with PPIs without any significant improvement. Itopride was added to the PPI therapy in a dose of 150 mg/day, after which the severity of reflux disease symptoms was reassessed. Results: The greatest improvement after the combined treatment (p < 0.001) was experienced in the context of heartburn, nausea and laryngopharyngeal symptoms. There was also a high percentage of statistically significant (p < 0.01) improvement in burning in the oesophagus and stomach and regarding postprandial fullness, gastric retention and swallowing disorders. No adverse effects were noted. Conclusions: The presented study clearly demonstrates that in patients ineffectively treated with PPIs, the addition of itopride to the therapy for 8 weeks without changing the PPI dose, significantly improves the efficacy of treatment of reflux disease and thus shortens the need for medication usage and reduces the costs of therapy, potential side effects of PPI, improves the patient's quality of life and decreases the frequency of medical appointments.

Effect of on-demand vs continuous prescription of proton pump inhibitors on symptom burden and quality of life: results of a real-world randomized controlled trial in primary care patients with gastroesophageal reflux disease.

OBJECTIVES: This study aimed to assess the impact of on-demand versus continuous prescribing of proton pump inhibitors (PPIs) on symptom burden and health-related quality of life in patients with gastroesophageal reflux disease (GERD) presenting to primary care. METHODS: Thirty-six primary care centres across Europe enrolled adult GERD patients from electronic health records. Participants were randomised to on-demand or continuous PPI prescriptions and were followed for 8 weeks. PPI intake, symptom burden, and quality of life were compared between the two groups using mixed-effect regression analyses. Spearman's correlation was used to assess the association between changes in PPI dose and patient-reported outcomes. RESULTS: A total of 488 patients (median age 51 years, 58% women) completed the initial visit, with 360 attending the follow-up visit. There was no significant difference in PPI use between the continuous and on-demand prescription groups (b=.57, 95%CI:0.40-1.53), although PPI use increased in both groups (b = 1.33, 95%CI:0.65 - 2.01). Advice on prescribing strategy did not significantly affect patient-reported outcomes. Both symptom burden (Reflux Disease Questionnaire, b=-0.61, 95%CI:-0.73 - -0.49) and quality of life (12-item Short Form Survey physical score b = 3.31, 95%CI:2.17 - 4.45) improved from baseline to follow-up in both groups. Increased PPI intake correlated with reduced reflux symptoms (n = 347, ρ=-0.12, p = 0.02) and improved quality of life (n = 217, ρ = 0.16, p = 0.02). CONCLUSION: In real-world settings, both continuous and on-demand PPI prescriptions resulted in similar increases in PPI consumption with no difference in treatment effects. Achieving an adequate PPI dose to alleviate reflux symptom burden improves quality of life in GERD patients. EudraCT number 2014-001314-25.

Continuous and on-demand prescription increase in proton pump inhibitor consumption equally in real-world settings and did not result in different outcomes.Reaching a sufficient dose of proton pump inhibitor to reduce reflux symptom burden improves quality of life in patients with gastroesophageal reflux disease.

Diagnostic and therapeutic management in gastroesophageal reflux disease: consensus of the Polish Society of Gastroenterology.

The paper was prepared by an expert group appointed by the Polish Society of Gastroenterology with an aim to update and systematize the knowledge about diagnosis and treatment of gastroesophageal reflux disease (GERD). Based on the previously published guidelines of international societies, expert consensuses, and recently published good quality data, we formulated 74 statements regarding the definition, diagnosis and treatment of GERD and assessed the level of acceptance of these statements and the reliability of the data. We discussed in details the possibilities and limitations of the available diagnostic methods and therapies, with particular emphasis on the diversity of gastroesophageal reflux symptoms and complications including Barrett's esophagus. Practical principles regarding interpretation of the diagnostic tests are presented. In addition, we discussed the indications for surgical treatment as well as the situations in which surgical treatment is not indicated with emphasis on the importance of preoperative diagnostics. The role of add-on therapy and indications for maintenance treatment are defined.

Esophageal Motility Disorders in the Natural History of Acid-Dependent Causes of Dysphagia and Their Influence on Patients' Quality of Life-A Prospective Cohort Study.

BACKGROUND: Esophageal dysmotility may be the cause or a secondary effect of gastric acid-dependent diseases: erosive reflux disease (ERD), Schatzki ring (SR) and eosinophilic esophagitis (EoE). METHODS: This study aims to compare concomitant dysphagia with ERD, SR and EoE, considering manometric patterns, their role in the natural history and their impact on assessing quality of life. Fifty-eight patients with dysphagia underwent high-resolution manometry and esophago-gastro-duodenoscopy (EGD) with an assessment of SR, ERD and sampling for EoE, completed a questionnaire with the Eating Assessment Tool (EAT-10) and the Gastrointestinal Quality of Life Index. Based on endoscopic images and the histopathological criterion of EoE (≥15 eosinophils/high-power field), patients were assigned to groups with ERD, EoE, SR and with normal endoscopic and histopathological images. In the data analysis, p ≤ 0.05 was considered statistically significant. This trial was registered with ClinicalTrials.gov (no. NCT04803162). RESULTS: Both EoE, SR and ERD correlate with ineffective motility. In ERD, normal peristalsis precedes the development of the disease, unlike EoE, which develops later and leads to absent contractility. The development of SR is associated with disorders of the upper esophageal sphincter (UES). In the group with SR and ERD, UES insufficiency significantly reduces the quality of life. Patients with normal esophagus in EGD scored the lowest quality of life and those with SR had the most severe dysphagia. CONCLUSION: The esophageal motility disorders co-occurring with endoscopic and histological anomalies do not significantly affect the severity of dysphagia, however, in the case of patients with ERD and SR and concomitant UES insufficiency, this motor dysfunction has a significant impact on the reduction in the patients' quality of life. Although no specific esophageal motility pattern typical of EoE, ERD and SR has been identified, comparative assessment of manometric features may have a potential role in differential diagnosis.

Association between Schatzki ring and eosinophilic esophagitis: a systematic review and meta-analysis.

BACKGROUND/OBJECTIVE: The involvement of hydrochloric acid in the etiology of eosinophilic esophagitis and numerous reports on its coexistence and interaction with reflux disease, as well as the rings of the esophageal mucosa formed with the advancement of the disease, suggest a potential association of eosinophilic esophagitis with another disorder of esophageal morphology potentially caused by exposure to acid reflux-Schatzki ring. Therefore, it seems reasonable to check the relationship of eosinophilic esophagitis with the coexistence of the Schatzki ring as a potential effect of advanced esophageal trachealization, which is the subject of this systematic review with a meta-analysis. METHODS: The protocol of this meta-analysis was performed according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. A systematic search of the indexed literature in the MEDLINE and Scopus databases from early to December 2019 was performed to identify all original research articles on the association between the occurrence of the Schatzki ring and eosinophilic esophagitis in adults. RESULTS: Out of 68 searched studies, after the analysis and evaluation of the works, only 4 met the criteria set according to the protocol and were included in the meta-analysis. Based on the performed meta-analysis, no relationship was found between the occurrence of Schatzki ring and eosinophilic esophagitis. CONCLUSION: The present study did not show a significant relationship between the occurrence of the Schatzki ring and eosinophilic esophagitis in the adult population, which suggests that these are two independent causes of dysphagia in this patient population.

Association of eosinophil-mediated inflammatory biomarkers with the presence of the Schatzki ring.

PURPOSE: The study aimed to assess the level of inflammatory biomarkers related to eosinophilia: interleukins 5 (IL-5) and 13 (IL-13), eotaxin 3, major basic protein (MBP) and transforming growth factor ß1 (TGF-ß1) in patients with dysphagia and Schatzki ring (SR), as well as the characteristics of this group of patients in terms of the features differentiating gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE). PATIENTS AND METHODS: We analyzed 42 patients with dysphagia, each of whom underwent panendoscopy with an assessment of the occurrence of SR, retrospectively assessed EoE Endoscopic Reference Score (EREFS) total, inflammatory and fibrostenotic and serum concentrations of IL-5 and 13, TGF-ß1, eotaxin 3 and MBP. All of them completed a symptom and comorbid questionnaire. Patients diagnosed with SR constituted the SR group (n â€‹= â€‹8), the rest - the non-SR group. The quantification of the biomarkers was performed by enzyme immunoassay (ELISA). In the data analysis, p â€‹≤ â€‹0.05 was considered statistically significant. RESULTS: We demonstrated a significant increase in terms of exceeding the reference values of TGF-ß1 (37.5% vs 8.8%) and MBP (75% vs 35.3%) in patients with SR compared to the non-SR group (qualitative analysis). There was also a statistically significant increase in the concentration of each of the determined biomarkers (quantitative analysis) in the SR group. CONCLUSIONS: The increase in TGF-ß1 and MBP concentrations indicates the inflammatory and probably fibrostenotic pathogenesis of SR. Obtained results do not allow for an unequivocal classification of SR as a complication typical only for GERD or EoE.

Searching for Noninvasive Predictors of the Diagnosis and Monitoring of Eosinophilic Esophagitis-The Importance of Biomarkers of the Inflammatory Reaction Involving Eosinophils.

BACKGROUND: Invasive and costly endoscopic diagnosis is obligatory for the diagnosis and monitoring of eosinophilic esophagitis (EoE). This study aims to evaluate the usefulness of serum biomarkers involved in eosinophil-mediated inflammation in the management of EoE. METHODS: A prospective cohort study was conducted in 58 patients with dysphagia. Each participant completed a health questionnaire, underwent esophagogastroduodenoscopy with esophageal biopsy for histopathological examination and assessment of total, inflammatory and fibrostenotic Eosinophilic Esophagitis Reference Score (EREFS). Serum levels of interleukin 5 (IL-5), interleukin 13 (IL-13), transforming growth factor ß1 (TGF-ß1), major basic protein (MBP), and eotaxin 3 were determined by enzyme immunoassays. Total of 16 patients meeting the histological criteria for EoE were treated with proton pump inhibitors for 8 weeks, and then the same diagnostics was performed again. RESULTS: Statistically significantly higher concentrations of MBP and TGF-ß1 were demonstrated in the group of patients with EoE, while MBP and eotaxin 3 correlated with the peak eosinophil count (PEC). Baseline MBP levels and eotaxin 3 after treatment significantly positively correlated with EREFS. There was a negative correlation between IL-13 and fibrostenotic EREFS. Additionally, after treatment, a negative correlation TGF-ß1 was noted with the inflammatory EREFS and a positive correlation with the fibrostenotic EREFS. CONCLUSIONS: The potential role of MBP in predicting the diagnosis of EoE, eotaxin 3 in predicting the advancement and correlation of IL-13 and TGF-ß1 in differentiating the inflammatory and fibrotic course of the disease may facilitate the management and individualization of EoE therapy.

Gastroesophageal reflux disease - from the point of view of a gastroenterologist, otolaryngologist and surgeon.

Gastrooesophageal reflux disease is the regurgitation of stomach contents into the esophagus, which causes troublesome symptoms or complications for the patient. Before starting the treatment, it is always necessary to objectively confirm gastroesophageal reflux disease, especially in correlation with ENT symptoms, as extra esophageal complications. In diagnostics, the "gold standard" is a 24-hour impedance-pH supplemented with endoscopy. Treatment without objective confirmation of the disease is not recommended, the more so that non-acid gas proximal reflux, detectable only in the MIIpH test, causes the greatest number of laryngological complications. It is important to confirm the coexistence of clinical symptoms of GERD with ESS. Considering the time of treating the disease and its consequences, it is worthwhile to be cautious and careful with the diagnosis of the disease, and the treatment should be carried out for a long time in relation to the recommendation, preferably in cooperation with an ENT specialist and gastroenterologist. The greatest therapeutic effectiveness is achieved by combining PPI with itopride while maintaining the appropriate doses of drugs and observing a sufficiently long duration of treatment, while maintaining the correct dose reduction and drug discontinuation regimen. In case of failure of pharmacological treatment, antireflux surgery should be take into consideration.

High-resolution manometry in diagnostics and evaluation of therapy effectiveness in patients with eosinophilic esophagitis - underestimated breakthrough or dead end?

Eosinophilic esophagitis (EoE) is a chronic disease with non-specific symptoms, among which dysphagia is a prevailing one. The observed increase of EoE rate, its chronic and recurrent character, as well as invasive follow-up examination (periodical panendoscopy with specimen collection for histopathology), compel optimization of both the diagnostics algorithm and disease monitoring through searching for new, unique methods and tools so far not applied, including high-resolution manometry (HRM). Mentioned investigations result from advances in comprehension of disease pathogenesis, in which it is suggested that development of a chronic inflammatory reaction of the esophageal wall may lead to consecutive fibrosis and motility disorders. In research published to date one manometric pattern characteristic for EoE was not obtained, whereas the obtained inconsistent and at times contradictory results do not correlate either with symptoms exacerbation or endoscopic scan. Numerous constraints of discussed studies as well as current knowledge in disease etiopathology and esophagus biomechanics prompt further investigation of HRM significance in diagnostics and therapy monitoring of patients with EoE.

The relationship between gastroesophageal reflux disease and the level of physical activity.

PRINCIPLES: Data on associations between physical activity and gastroesophageal reflux disease (GERD) have been inconsistent. Although experimental and clinical studies prove that exercise increases gastroesophageal reflux, epidemiological observations on the relationship between GERD and everyday physical effort deliver contradictory results. Our aim was to examine the association between the level of everyday physical activity and parameters of the disease (pH-metry, symptoms) in patients diagnosed with GERD. METHODS: We assessed the level of physical activity in a survey of 100 consecutive GERD patients. All subjects had undergone 24-h pH monitoring in a tertiary setting and reported symptoms they experienced daily. Using the criteria of the short form of the International Physical Activity Questionnaire (7-day recall) we identified groups presenting with low (I), moderate (II) or high (III) levels of physical activity. The amount of physical activity was expressed as multiples of resting metabolic rate and minutes of performance during a week (METs-minute/week). For evaluation of relationships between everyday physical activity and pH-metric indices of GERD a multivariate regression analysis was performed. The parameters studied were adjusted for age, BMI, smoking and gender (as covariates). RESULTS: We did not observe any association between the amount of everyday physical activity (expressed as log base 10 METs-minute/week) and pH-metric parameters of GERD evaluated 5 cm and 15 cm above the lower oesophageal sphincter (LES). Furthermore, we analyzed relationships between investigated parameters and covariates: age, BMI, smoking and gender. We found significant correlations only between the number of reflux episodes 15 cm above LES and gender (beta -0.25; p <0.05) and between the number of reflux episodes 5 cm above LES and age (beta -0.24; p <0.05). The number of self-reported symptoms did not differ among the three groups of physical activity level. It reached 6 in groups I and II, and 7 in group III (p = 0.07). However we must note that we found a weak, positive correlation between the number of symptoms reported by patients and METs-minute/week (r = 0.21, p <0.05). CONCLUSIONS: In view of our results the level of everyday physical activity is not associated with symptoms of GERD. This observation should be confirmed in other populations with GERD diagnosed upon pH-metric criteria.

Gastroesophageal reflux disease and physical activity.

Gastroesophageal reflux disease (GERD) is one of the most common disorders in the general population. In recent years, a marked increase in the occurrence of the disease worldwide has been noted. Intense exercise belongs to factors that are known to exacerbate symptoms of GERD. Episodes of reflux seem to be associated with the length and the intensity of the physical activity undertaken. Experimental studies suggest that the gastroesophageal reflux may be increased in athletes due to: decreased gastrointestinal blood flow; alterations of hormone secretion; changes in the motor function of the oesophagus and the ventricle; and the constrained body position during exercise. Disturbances of the balance between two areas of opposite pressure: intra-abdominal and intrathoracic, have also been proven to influence GERD events. GERD is found in sportspeople of various disciplines, but specific types of exercise may have significantly different impacts on the gastroesophageal reflux.Basic prevention of GERD comprise lifestyle and dietary interventions. Adjustments of the exercise load and avoiding meals and drinks about the time of physical effort may ease the symptoms. Unfortunately, in most patients, pharmacological measures are necessary. These include occasional application of antacids and blockers of histamine H2 receptors in mild forms of the disease, and a regular therapy with proton pump inhibitors (PPI) in the majority of other cases. An average dose of PPI varies from 20 to 40 mg/day and should be continued for 4-8 weeks. Unfortunately, symptoms of GERD frequently return and in these situations long-term acid suppression with PPI is usually necessary. As regular physical activity exerts beneficial health effects, the necessity of establishing associations between moderate, recreational exercise and GERD is needed.

[Laryngeal symptoms in patients with gastroesophageal reflux diseases]. / Objawy laryngologiczne u chorych z choroba refluksowa przelyku.

Gastroesophageal reflux disease (GERD) is considered an important etiological factor of numerous larynx dysfunctions. The goal of our study was to describe larynx status of patients with GERD before and after treatment. Forty-five patients with GERD symptoms entered our study. GERD was confirmed in 24-hours pH-metric examination. Patients were treated with proton pump inhibitors in doses chosen accordingly to GERD severity. All patients underwent endoscopic evaluation of the larynx and acoustic voice analysis before and after the treatment. GERD was diagnosed in 35 out of 45 patients. Acoustic voice analysis revealed that voice disorders appeared more often in patients with severe than moderate or mild refluxes (p = 0.023). Laryngeal changes found in endoscopic evaluation also depended on reflux severity (p = 0.05). The voice quality improved (p = 0.031) and the changes in larynx diminished after anti-reflux treatment (p = 0.016).

Associations between the lower esophageal sphincter function and the level of physical activity.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a very frequent and multifactorial disease. It has been found that GERD is associated with obesity, smoking, esophagitis, diet and lifestyle. Physical activity is among the factors involved in the occurrence of GERD. OBJECTIVES: The aim of the study was to evaluate the associations between the different parameters of lower esophageal pressure (LES) and the level of everyday physical activity in patients with GERD. MATERIAL AND METHODS: The authors examined 100 consecutive patients who underwent manometry and pH-metry because of symptoms suggesting GERD. Physical activity was assessed by means of the International Physical Activity Questionnaire (IPAQ). In accordance with IPAQ categorical scoring, the authors divided the studied subjects into 3 groups according to their level of physical activity. The investigation comprised 59 men and 41 women, with the mean age 49 ± 14 years. RESULTS: The authors analyzed the relationships between the LES parameters (pressure, total LES length and HPZ length) and physical activity. The authors did not find any significant correlations between the studied parameters and the amount of physical activity. The authors also did not observe any association between the LES pressure and the level of physical activity. The subgroups distinguished on the basis of LESP did not differ as to the amount of everyday physical activity as well. CONCLUSIONS: Although most data indicates that intense exercise exacerbates GERD symptoms, the authors did not find any associations between LES parameters and physical activity. In view of the present results maintaining the recommended level of everyday physical activity does not interfere with the mechanisms of GERD.

The influence of deficiencies of essential trace elements and vitamins on the course of Crohn's disease.

In patients with Crohn's Disease (CD), malnutrition is frequently observed and is an important complication, frequently associated with nutritional deficiencies, especially vitamins (both water- and fat-soluble) and essential trace elements. It is often a result of the disease activity, poor oral intake and/or restrictive diets. Nutrition plays an important role in disease management and helps to maintain remission in CD patients. Deficiencies occur in patients with active Crohn's disease, and also in those in remission. Specific supplementation of vitamins and micro- and macronutrients might be helpful or even necessary in this group of patients. This review outlines the most frequent nutritional deficiencies and their complications in relation to the Crohn's Disease Activity Index, and provides an overview of therapeutic perspectives for CD patients in adult patients with inflammatory bowel disease (IBD). Biological therapy, which is being used with increasing frequency, seems not only to mitigate the inflammatory process in the gastrointestinal tract, but also has significant impact on the nutritional status of patients with Crohn's disease.